(2R)-4-methyl-2-[2-oxo-2-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]ethyl]pentanenitrile | 910248-67-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (2R)-4-methyl-2-[2-oxo-2-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]ethyl]pentanenitrile
• CAS: 910248-67-8
• 化学式: C₁₄H₂₂N₂O₃
• 分子量: 266.34
• InChiKey: WRBJDNKWDCWXRA-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  70.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R)-4-methyl-2-[2-oxo-2-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]ethyl]pentanenitrile 在 platinum(IV) oxide 盐酸 、 氢气 作用下， 以 乙醇 为溶剂， 反应 90.0h， 生成 (R)-3-(aminomethyl)-5-methylhexanoic acid hydrochloride
  参考文献：
  名称：

  Diastereoselective Conjugate Addition of Cyanide to α,β-Unsaturated ­Oxazolidinones: Enantioselective Synthesis of ent-Pregabalin and Baclofen

  摘要：

  手性α,β-不饱和恶唑啉酮的氰基共轭加成反应在钐(III)异丙氧化物催化下进行，具有良好的非对映选择性。加成产物可转化为生物活性目标药物ent-普瑞巴林和巴氯芬。

  DOI：

  10.1055/s-2006-941584
• 作为产物：
  描述：

  (4S)-3-[(E)-5-methylhex-2-enoyl]-4-propan-2-yl-1,3-oxazolidin-2-one 、 丙酮氰醇 在 samarium(III) isopropoxide 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以66%的产率得到(2R)-4-methyl-2-[2-oxo-2-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]ethyl]pentanenitrile
  参考文献：
  名称：

  Diastereoselective Conjugate Addition of Cyanide to α,β-Unsaturated ­Oxazolidinones: Enantioselective Synthesis of ent-Pregabalin and Baclofen

  摘要：

  手性α,β-不饱和恶唑啉酮的氰基共轭加成反应在钐(III)异丙氧化物催化下进行，具有良好的非对映选择性。加成产物可转化为生物活性目标药物ent-普瑞巴林和巴氯芬。

  DOI：

  10.1055/s-2006-941584

文献信息

• Process for the enantioselective preparation of pregabalin
  申请人：Laboratorios del Dr. Esteve S.A.

  公开号：EP2017273A1

  公开（公告）日：2009-01-21

  The invention provides a new enantioselective process for the preparation of (S)-pregabalin, or a pharmaceutical acceptable addition acid salt comprising: acid hydrolysis of the dioxolan ring of a chiral compound of general formula (I) to obtain compound of general formula (II); oxidation of compound (II) to obtain a compound of general formula (III) and transforming compound (III) into compound of general formula (IV); subjecting compound (IV) to basic hydrolysis to obtain a compound of general formula (V) which is reduced to obtain enantiomerically pure S-pregabalin. The invention also provides new chiral intermediates involved in the process.

  本发明提供了一种新的对映选择性过程，用于制备（S）-普瑞巴林，或制备药物可接受的加酸盐，包括：将手性化合物的二氧兰环进行酸水解，得到通式（II）的化合物；将化合物（II）氧化得到通式（III）的化合物，并将化合物（III）转化为通式（IV）的化合物；将化合物（IV）进行碱性水解得到通式（V）的化合物，然后还原得到对映纯的S-普瑞巴林。本发明还提供了参与该过程的新手性中间体。
• PROCESS FOR THE ENANTIOSELECTIVE PREPARATION OF PREGABALIN
  申请人：Ortuno Rosa M.

  公开号：US20100197939A1

  公开（公告）日：2010-08-05

  The invention provides a new enantioselective process for the preparation of (S)-pregabalin, or a pharmaceutical acceptable addition acid salt comprising: acid hydrolysis of the dioxolan ring of a chiral compound of general formula (I) to obtain compound of general formula (II); oxidation of compound (II) to obtain a compound of general formula (III) and transforming compound (III) into compound of general formula (IV); subjecting compound (IV) to basic hydrolysis to obtain a compound of general formula (V) which is reduced to obtain enantiomerically pure S-pregabalin. The invention also provides new chiral intermediates involved in the process.

  本发明提供了一种新的对映选择性工艺，用于制备（S）-普瑞巴林，或其药物可接受的酸盐，包括：对手性化合物（I）的二氧六环环的酸水解，以获得通式（II）的化合物；将化合物（II）氧化，以获得通式（III）的化合物，并将化合物（III）转化为通式（IV）的化合物；将化合物（IV）进行碱性水解，以获得通式（V）的化合物，然后还原化合物（V）以获得对映纯的S-普瑞巴林。本发明还提供了涉及该过程的新手性中间体。
• [EN] PROCESS FOR THE ENANTIOSELECTIVE PREPARATION OF PREGABALIN<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION ÉNANTIOSÉLECTIVE DE LA PRÉGABALINE
  申请人：ESTEVE LABOR DR

  公开号：WO2009010554A1

  公开（公告）日：2009-01-22

  The invention provides a new enantioselective process for the preparation of (S) -pregabalin, or a pharmaceutical acceptable addition acid salt comprising: acid hydrolysis of the dioxolan ring of a chiral compound of general formula (I) to obtain compound of general formula (II); oxidation of compound (II) to obtain a compound of general formula (III) and transforming compound (III) into compound of general formula (IV); subjecting compound (IV) to basic hydrolysis to obtain a compound of general formula (V) which is reduced to obtain enantiomerically pure S-pregabalin. The invention also provides new chiral intermediates involved in the process.
• Diastereoselective Conjugate Addition of Cyanide to α,β-Unsaturated ­Oxazolidinones: Enantioselective Synthesis of <i>ent</i>-Pregabalin and Baclofen
  作者：Alan Armstrong、Nicola Convine、Matthew Popkin

  DOI：10.1055/s-2006-941584

  日期：2006.6

  Conjugate addition of cyanide to chiral α,β-unsaturated oxazolidinones catalyzed by samarium(III) isopropoxide proceeds with good diastereoselectivity. The addition products can be ­converted into the biologically active targets ent-pregabalin and ­baclofen.

  手性α,β-不饱和恶唑啉酮的氰基共轭加成反应在钐(III)异丙氧化物催化下进行，具有良好的非对映选择性。加成产物可转化为生物活性目标药物ent-普瑞巴林和巴氯芬。